HARMONIC’s Fifth and Last Annual Meeting Shows Great Progress

The HARMONIC consortium held its fifth and final annual meeting on 28-29 May in Leuven, Belgium to discuss progress made by each Work Package (WP) and next steps, including how to ensure the sustainability of some of the project’s outputs beyond its completion in November 2024.

“I am happy to say that the consortium has accomplished a tremendous amount of work, despite the COVID-19 pandemic and the legal and technical challenges of sharing data between partners in different countries,” says Isabelle Thierry-Chef, Principal Investigator of HARMONIC. The EU-funded project aims to understand the late health effects of childhood exposure to ionising radiation, with a particular focus on young cancer patients exposed to photon or proton radiotherapy and on children exposed to X-rays during cardiac procedures.

Progress made

Established cohorts and databases: One of the main achievements of Harmonic has been the establishment of a European registry, complemented by a biobank, of children treated with photon or proton radiotherapy. More than 2000 cancer patients from the different partner centres have been included in the registry, with three of the centres still recruiting. Data are collected with a specific format in two linked databases: one contains encrypted clinical and socioeconomic data of the patient; the other contains imaging data. Biological samples (blood and saliva) of some of these patients have also been collected in a biobank. Analysis of all these data will help to understand the overall impact of the disease and its treatment on the patients’ quality of life, and to identify late health effects of exposure to photon or proton therapy, including endocrine dysfunction, cardiovascular or neurovascular damages, and the occurrence of other cancers later in life. Follow up of these patients is expected to last until 2041. “Our aim is to maintain this database for the five research centres of the consortium beyond the duration of the project, to ensure the follow-up of included participants and continue recruiting new ones,” explains Neige Journy, WP2 leader. “If possible, we also want to extend the database to other centres and enable the use of the registry to support other studies and collaborations,” she adds.

Another key achievement has been to build new cohorts – or expand existing ones – of children exposed to X-rays during cardiology interventions, and to link these data with national cancer registries in order to estimate the risk of developing cancer later in life. Data from over 66,000 patients (including previously collected data in the UK) have been collected in Belgium, France, Germany, Italy, Norway and Spain and are currently being pooled for analysis by WP3 researchers.

Validated tools for dosimetry: In order to link late health effects to radiation exposure in these two cohorts, it is necessary to estimate the radiation doses received by each patient, not only in the target area but also in the rest of the body. The tools for this whole-body dose reconstruction, for both radiotherapy and interventional cardiology, have been developed and validated by WP4. The research team can now retrospectively estimate whole-body dose distributions for patients in the two cohorts and associate dose exposure with health outcomes. WP4 also developed a web-based software that uses mixed reality to help paediatric cardiologists make decisions before the intervention and optimise radiation doses.

Identifying mechanisms and biomarkers: The WP5 team has begun analysing blood samples from the two patient cohorts to identify biological pathways that may lead to late health effects, in particular vascular damage and second primary cancer. Among other things, they are looking at plasma protein profiles, cellular ageing, and altered gene expression. “By analysing samples taken before and up to one year after exposure, we hope to identify biomarkers of late effects,” says Siamak Haghdoost, WP5 leader.

Next steps

In the remaining six months, the consortium will complete the data collection and analysis. Given that data sharing between countries has been one of the biggest challenges during the project, the consortium also intends to make some recommendations on how to make this easier in the future, while ensuring patient privacy. 

The HARMONIC team strongly believes that these databases should be maintained beyond the project’s lifetime, as many of the late health effects, such as second primary cancers, take many years to appear. “We have invested a lot of effort and resources to build a working registry of paediatric cancer patients with a structure that can be used by other centres, and our two cohorts are extremely valuable for long-term follow-up as they include children exposed to different doses and types of radiation,” says Thierry-Chef.